幼儿糖尿病伴急性外阴阴道炎1例报告

1 病例报告 女,6岁。因外阴瘙痒伴烧灼感,排尿时疼痛加重4天来诊。妇检;外阴皮肤见明显搔抓痕迹,整个外阴及肛门周围明显充血水肿,阴道口充血更加明显见白色较稠分泌物,量中等。取分泌物涂片查见假菌丝。诊断:幼儿外阴—阴道炎。用2％小苏打冲洗外阴后复方制霉菌素霜(本院自制)外涂外阴部并用KS微波治疗仪照射外阴。经综合治疗2天后瘙痒及外阴部皮肤充血减轻。继续治疗1周后才发现患儿多饮多尿。查尿:尿     

聚焦超声治疗38例外阴白色病变临床分析

目的:目的:探讨聚焦超声治疗外阴白色病变的可行性和有效性。方法:采用超声监测和组织病理学检查相结合的方法观察38例经病理检查证实为外阴白色病变的患者聚焦超声治疗期间及治疗后症状、体征及局部组织结构的变化。结果:聚焦超声治疗后,患者的局部瘙痒症状明显缓解甚至完全消失,外阴的形态和色泽基本恢复正常,治疗有效率达94.7%。治疗后局部皮肤的表皮完整,真皮组织有一过性的充血、水肿,水肿的高峰期在治疗后的24～48 h,以后逐渐消退,至治疗后7～10天恢复正常。治疗后l个月复查,外阴白色病变部位的皮肤逐渐恢复正常形态,并有色素沉着,局部表皮保持完整。聚焦超声治疗前后的病理检查结果显示:治疗后表皮及真皮层组织结构均逐渐恢复正常,基底层细胞色素沉积,真皮内的微血管明显增多,且管腔形态正常,浸润的淋巴细胞数量明显减少。结论:聚焦超声用于治疗外阴白色病变安全、有效,是治疗外阴白色病变的新方法。     

T淋巴细胞和血管内皮细胞在外阴白色病变中的变化

目的 探讨T淋巴细胞和血管内皮细胞在外阴白色病变的发生、发展及聚焦超声治疗中的作用.方法 收集40例外阴皮肤标本(20例外阴白色病变为病变组,其中鳞状上皮增生型12例.硬化性苔藓型8例;20例经病理证实为正常外阴皮肤为对照组),病变组均经聚焦超声治疗,其中11例治疗后重取标本,均采用免疫组化法对标本中的T淋巴细胞和血管内皮细胞进行检测.结果 病变组患者病损皮肤与对照组相比CD4+、CD8+T淋巴细胞减少,CD4,CD8比值减小,CD34+血管内皮细胞减少.经聚焦超声治疗后,CD4+、CD8+T淋巴细胞及CD34+血管内皮细胞增加.结论 T淋巴细胞和血管内皮细胞在外阴白色病变的发生、发展及聚焦超声治疗中发挥重要作用.     

CD34在外阴白色病变组织中的表达及临床意义

目的:研究外阴白色病变组织中微循环状况,探讨外阴白色病变的发病机制。方法:对来医院就诊的均于阴道镜下病变明显处取活组织病理检查,证实为外阴白色病患者41例,采用免疫组织化学方法检测在41例外阴白色病变(其中鳞状上皮增生22例,硬化性苔藓19例)组织中CD34的表达情况,8例正常的外阴组织做对照。结果:外阴硬化性苔藓的微血管数目(MVD值)显著低于正常外阴组,差异有统计学意义(P<0.05),外阴鳞状上皮增生与正常外阴组织相比差异无统计学意义(P>0.05),且硬化性苔藓(LS组)与鳞状上皮增生(SH组)之间存在显著性差异,硬化性苔藓MVD值低于鳞状上皮增生。结论:外阴硬化性苔藓组织中微血管数目减少明显,鳞状上皮增生中血管数目无明显改变。     

bFGF、FGFR-1在外阴鳞状上皮增生组织中表达及意义

目的分析聚焦超声（HIFU）治疗对外阴鳞状上皮细胞增生组织中bFGF和FGFR-1表达的影响,探讨其可能的治疗机制。方法采用免疫组化SABC法,检测30例患者治疗前后外阴鳞状上皮细胞增生组织中碱性成纤维细胞生长因子（bFGF）及其受体成纤维细胞生长因子受体-1（FGFR-1）的表达。结果外阴鳞状上皮细胞增生病损区皮肤bFGF及FGFR-1表达均较正常皮肤组织明显降低（分别为16.7%、46.7%）,差异有统计学意义（P〈0.05）,聚焦超声治疗后1月,bFGF及FGFR-1的表达均较治疗前显著增高（分别为86.7%、80%）（P〈0.01）,患者治疗后3个月病变部位bFGF、FGFR-1表达与外阴正常部位皮肤及正常女性外阴皮肤比较差异无统计学意义（P〉0.05）。结论 1.HIFU能有效提高组织中bFGF、FGFR-1的表达,可能是治疗外阴鳞状上皮细胞增生的分子机制之一。2.bFGF、FGFR-1表达的降低可能与外阴鳞状上皮细胞增生的发病有关。     

高功率微波辐照对大鼠睾丸形态和超微结构的影响

目的 观察高功率微波(HPM)辐照后大鼠睾丸病理形态变化特征。方法 健康成年雄性SD大鼠45只,随机分为8个实验组和1个对照组。以S波段功率密度分别为20 mW·cm-2、40mW·cm-2的HPM辐照实验组大鼠,辐照时间分别为1、5、10和20 min。于辐照后6 h取材,以透射电镜和光镜观察其病理形态变化。结果 光镜下与对照组相比,20 mW·cm-25 min组开始出现轻度炎细胞浸润、组织充血,水肿;10 min组出现生精上皮细胞排列紊乱,畸形精子增多;20 min组和40 mw·cm-21 min组可见大鼠睾丸部分曲细精管管腔断裂,生精细胞明显坏死脱落。上述改变随功率密度增加,照射时间延长而加重。40 mW·cm-2 5 min组部分曲细精管内几乎无细胞,损伤达坏死极限;电镜下超微结构发生轻度线粒体水肿和内质网扩张是从20 mW·cm-25 min组开始,10 min组可见精原细胞水肿变性,20 min组毛细血管内皮细胞肿胀,基底膜分层,断裂。精原细胞凋亡增多,线粒体呈空泡化。功率增高后的各组均可见部分间质细胞发生变性、凋亡和坏死崩解。对照组无改变。结论 高功率微波辐照可导致大鼠睾丸形态发生明显的病理性改变,当达到20 mW·cm-2 20 min或40mW·cm-21 min后,对大鼠睾丸组织细胞有致死作用。     

聚焦超声治疗外阴白色病变疗效观察

目的:观察聚焦超声治疗外阴病变的疗效。方法:对2004年1~12月就诊的150例外阴白色病变患者在排除外阴癌前病变及外阴、阴道急性炎症后采用海极星聚焦超声治疗系统进行治疗。结果:术后外阴瘙痒症状消失或减轻,外阴皮肤颜色逐渐恢复正常,弹性好转,组织结构恢复正常。3个月后复查,95%的患者达到生理状态。结论:聚焦超声治疗外阴白色病变是目前较为理想的方法。     

抗栓Ⅱ号药与扩张血管药联合应用治疗兔足重度冻伤的效果研究

目的 :　探讨抗栓Ⅱ号药与局部血管扩张药联合应用治疗兔足重度冻伤的作用 ,为寻求较简便的冻伤治疗措施提供依据。方法 :将体重 2 .0～ 3.0kg大耳白家兔用 - 2 5℃乙醇冷冻及 2 0℃水复温的冻伤模型造成兔足重度冻伤。于伤后 4h开始按不同治疗方法分组 ,(1)对照组 :除每天更换纱布外 ,不予药物治疗 ;(2 )洗必泰组 :用洗必泰液多次温浸法治疗 ;(3)抗栓Ⅱ号组 :抗栓Ⅱ号静脉滴注加环丙沙星局部涂敷 ;(4 )综合治疗组 :以抗栓Ⅱ号为主 ,静脉滴注 ,同时局部多点注射利血平和妥拉苏林并外用环丙沙星。于冻伤前及冻伤后不同时期测量活存面积和足掌中心皮肤温度。结果 :(1)活存面积 :洗必泰组和综合治疗组兔足冻伤后的活存面积分别为(5 6.67± 2 8.96) %和 (60 .4 4± 2 8.11) %与对照组的 (19.37± 13.31) %有显著差异 (P <0 .0 1)抗栓Ⅱ号组的活存面积为 (2 5 .2 3± 12 .4 4 ) % ,与对照组无显著差异 (P <0 .0 5 )。 (2 )皮肤温度 :冻伤后第 2天各组兔足皮温都有所下降 ,但对照组和抗栓Ⅱ号组在第 5、12、2 1天时的皮温已经降至室温 (2 5℃ )水平 ,而洗必泰组和综合治疗组的皮温基本保持在 30℃左右的水平上 ,与对照组比较差异显著 (P <0 .0 1)。结论 :抗栓Ⅱ号和局部扩张血管药合用治疗兔足重度冻伤的效果     

大豆异黄酮抗辐射效果的观察

目的观察大豆异黄酮对60Co-γ射线照射后小鼠生长和外周血象的影响.方法按体重将80只雌性昆明小鼠随机均分为5组,即正常对照、阳性对照及低、中、高剂量大豆异黄酮实验组.辐照前正常对照、阳性对照组及实验组每天分别以溶剂0.5%羧甲基纤维素钠(CMC-Na)和不同剂量大豆异黄酮连续灌胃14 d,灌胃至第7天,除正常对照组外,其余各组小鼠均接受4.56Gy60Co-γ全身性照射1次,照射后继续灌胃2 d及7天后将动物处死,迅速取血,EDTA抗凝进行检测.结果实验结束时,中、高剂量大豆异黄酮组小鼠体重增重与正常对照无显著差别,但与单纯辐照组相比差别显著(P＜0.05);辐照后第7天,大豆异黄酮各实验组白细胞上升均高于单纯辐照组,中剂量实验组显著高于单纯辐照组(P＜0.05);仅中剂量大豆异黄酮组网织红细胞照后第7天明显上升,与第2天有明显差异(P＜0.01);血红蛋白、血小板及红细胞虽各组间无明显差异,但低、中剂量大豆异黄酮组血红蛋白与正常对照组相近;中剂量组血小板下降幅度在各受辐照组中最小;单纯辐照组红细胞低于各大豆异黄酮干预组,中剂量干预组最接近正常对照组.结论大豆异黄酮对受辐照小鼠的血液系统有一定的保护效果,以中剂量组效果较好,且可预防辐射对生长发育的不良影响.     

Ⅱ型减压病肺组织超微结构改变

目的观察兔实验型减压病肺组织超微结构改变,探讨减压病对肺组织损伤的机制。方法用雄性新西兰家兔制备减压病模型。动物出舱后30⁶0分钟内处死,取肺尖部组织,制备超薄切片,电镜下观察超微结构。并设安全减压组和正常组作为对照。结果减压病组:电镜下见肺泡腔部分闭塞,部分实性变,内见红细胞渗出,Ⅰ型肺泡上皮细胞突起回缩,胞体肿胀,线粒体肿胀。Ⅱ型肺泡上皮细胞肿胀明显,细胞质内线粒体扩张,板层小体减少;另见部分Ⅱ型上皮细胞固缩,核染色质凝集,固缩的细胞内线粒体空泡变性,板层小体消失。毛细血管扩张充血,毛细血管内皮细胞肿胀,基底膜不完整。安全减压组:部分肺泡腔扩大,毛细血管充血,Ⅰ性肺泡上皮和毛细血管内皮细胞轻度肿胀;Ⅱ型肺泡上皮线粒体轻度肿胀,溶酶体数目增多,板层小体细胞膜下聚集。结论减压病可导致呼吸上皮损伤、血气屏障破坏,影响肺泡气体交换;其机制可能与减压过程中,在血管和组织内产生的游离气泡有关。     

阿的平对高功率微波损伤小鼠睾丸的保护作用

目的:探讨阿的平对高功率微波辐射小鼠睾丸的保护作用。方法:雄性小鼠随机分为4组,即正常组、辐射对照组、阿的平低剂量组(12.6mg/kg)、阿的平高剂量组(50.4mg/kg)。小鼠分别灌胃给予注射用水和不同剂量阿的平后,使用频率2.856GHz、脉宽500ns的微波源,进行50mW/cm2的微波远场照射30min。于照射后即刻、1d、2d、7d取小鼠睾丸。将小鼠睾丸组织病理切片观察其形态学变化;组织蛋白匀浆法提取睾丸组织蛋白检测热休克蛋白(HSP)70表达变化。结果:微波照射小鼠30min后,辐射对照组的睾丸组织从即刻至7d均有病理改变,曲精小管边缘不整齐,生精细胞水肿,排列紊乱,间质充血。给药组与对照组相比曲精小管排列基本整齐,边缘清晰,生精上皮细胞肿胀较对照组减轻。其中给药低剂量组在照射即刻至2d改善效果与高剂量组相似,但在7d时高剂量组的改善效果明显优于低剂量组。Western blot结果显示,在照后2d阿的平高、低剂量给药组与辐射对照组相比HSP70蛋白表达升高,在7d时只有阿的平高剂量组与辐射对照组相比HSP70蛋白表达升高。结论:阿的平可能是通过上调HSP70蛋白的表达,发挥其抗炎和抗凋亡作用,从而对高功率微波致伤的小鼠睾丸组织产生保护作用。     

Radon exposure of the skin: I. Biological effects.

Radon progeny can plate out on skin and give rise to exposure of the superficial epidermis from alpha emitters Po-218 (7.7 MeV, range approximately 66 microm) and Po-214 (6 MeV, range approximately 44 microm). Dose rates from beta/gamma emitters Pb-214 and Bi-214 are low and only predominate at depths in excess of the alpha range. This paper reviews the evidence for a causal link between exposure from radon and its progeny, and deterministic and stochastic biological effects in human skin.Radiation induced skin effects such as ulceration and dermal atrophy, which require irradiation of the dermis, are ruled out for alpha irradiation from radon progeny because the target cells are considerably deeper than the range of alpha particles. They have not been observed in man or animals. Effects such as erythema and acute epidermal necrosis have been observed in a few cases of very high dose alpha particle exposures in man and after acute high dose exposure in animals from low energy beta radiations with similar depth doses to radon progeny. The required skin surface absorbed doses are in excess of 100 Gy. Such effects would require extremely high levels of radon progeny. They would involve quite exceptional circumstances, way outside the normal range of radon exposures in man.There is no definitive identification of the target cells for skin cancer induction in animals or man. The stem cells in the basal layer which maintain the epidermis are the most plausible contenders for target cells. The majority of these cells are near the end of the range of radon progeny alpha particles, even on the thinnest body sites. The nominal depth of these cells, as recommended by the International Commission on Radiological Protection (ICRP), is 70 microm. There is evidence however that some irradiation of the hair follicles and/or the deeper dermis, as well as the inter-follicular epidermis, is also necessary for skin cancer induction. Alpha irradiation of rodent skin that is restricted to the epidermis does not produce skin cancer. Accelerator generated high energy helium and heavy ions can produce skin cancer in rodents at high doses, but only if they penetrate deep into the dermis. The risk figures for radiation induced skin cancer in man recommended by the ICRP in 1990 are based largely on x and beta irradiated cohorts, but few data exist below absorbed doses of about 1 Gy. The only plausible finding of alpha-radiation induced skin cancer in man is restricted to one study in Czech uranium miners. There is no evidence in other uranium miners and the Czech study has a number of shortcomings.This review concludes that the overall balance of evidence is against causality of radon progeny exposure and skin cancer induction. Of particular relevance is the finding in animal studies that radiation exposure of cells which are deeper than the inter-follicular epidermis is necessary to elicit skin cancer. In spite of this conclusion, a follow-on paper evaluates the attributable risk of radon to skin cancer in the UK on the basis that target cells for skin cancer induction are the cells in the basal layer of the inter-follicular epidermis-since this is the conservative assumption made by international bodies such as the International Commission on Radiological Protection (ICRP) for general radiological protection purposes.     

高铁血红蛋白生成剂(MFA)对急性硫化氢中毒动物治疗作用的实验研究

目的 通过动物实验探讨MAF对急性硫化氢中毒的治疗作用。方法 将40只大鼠分为正常对照组、染毒对照组、美蓝求治组、4－DMAP救治组。以致死浓度的硫化氢染毒2min,对两组救治组动物分别给以美蓝和4－DMAP进行急救,2h后做相应生化及病理检查。结果 两救治组MHb、SMHb显著高于两对照组,4－DMAP组MHb、SMHb明显高于美蓝组;染毒对照组肺组织明显充血、水肿,两救治组主要表现为充血。结论 MFA对急性硫化氢中毒动物起到解毒作用,而4－DMAP效果优于美蓝。     

Prevention of mobile phone induced skin tissue changes by melatonin in rat: an experimental study

Most of the mobile phones in Turkey emit 900 MHz radiation which is mainly absorbed by the skin and, to a lesser extent, muscle. The aim of this study was to investigate the effects the 900 MHz electromagnetic irradiation emitted by these devices on the induction of histopathologic changes in skin and the effect of melatonin (Mel) on any of these changes. Thirty male Wistar-Albino rats were used in the study. The experimental groups were composed of: a nontreated control group, an irradiated group (IR) without Mel and an irradiated with Mel treatment group (IR + Mel). 900 MHz radiation was applied to IR group for 10 days (30 min/day). The IR + Mel group received 10 mg/kg per day melatonin in tap water for 10 days before irradiation. At the end of the tenth day, the skin graft was excized from the thoraco-abdominal area. Histopathologic changes in skin were analyzed. In the IR group, increased thickness of stratum corneum, atrophy of epidermis, papillamatosis, basal cell proliferation, increased granular cell layer (hypergranulosis) in epidermis and capillary proliferation, impairment in collagen tissue distribution and separation of collagen bundles in dermis were all observed compared to the control group. Most of these changes, except hypergranulosis, were prevented with melatonin treatment. In conclusion, exposure to 900 MHz radiation emitted by mobile phones caused mild skin changes. Furthermore, melatonin treatment can reduce these changes and may have a beneficial effect to prevent 900 MHz mobile phone-induced rat skin changes.     

Levels of retinyl palmitate and retinol in stratum corneum, epidermis and dermis of SKH-1 mice

Vitamin A (retinol) regulates many biological functions, including epidermal cell growth. Retinyl palmitate (RP) is the major esterified form of retinol and the predominant component of retinoids in the skin; however, how endogenous levels of RP and retinol in the skin are affected by the age of the animal remains unknown. Furthermore, the levels of retinol and RP in the various skin layers - the stratum corneum, epidermis and dermis of skin - have not been reported. In this paper, we report the development of a convenient method for separation of the skin from SKH-1 female mice into the stratum corneum, epidermis, and dermis and the determination of the levels of RP and retinol in the three fractions by HPLC analysis. The total quantities of RP and retinol from the stratum corneum, epidermis, and dermis are comparable to those extracted from the same amount of intact skin from the same mouse. There was an age-related effect on the levels of RP and retinol in the skin and liver of female mice. An age-related effect was also observed in the stratum corneum, epidermis, and dermis. The levels of RP and retinol were highest in the epidermis of 20-week-old mice, and decreased when the age increased to 60- and 68-weeks. The total amount of RP at 20 weeks of age was found to be 1.52 ng/mg skin, and decreased about 4-fold at 60- and 68-weeks of age. A similar trend was found for the effects of age on the levels of retinol.     

Echographic measurement of skin thickness in sites suitable for intradermal vaccine injection in infants and children

Whereas the knowledge of skin thickness is essential to determine microneedle length and ensure proper administration of and better responses to intradermal vaccines, very few figures are available, especially in infants and children. Using ultrasound echography, we investigated skin thickness in 384 children aged 4-7, 12-18, and 54-66 months at potential body sites for intradermal vaccine delivery: deltoid, suprascapular, upper back, and lumbar area. The mean epidermis plus dermis thickness was significantly higher at the suprascapular than at the deltoid site (1.29 mm vs. 1.22 mm) and remained relatively unchanged whatever the BMI, age, sex, and skin phototype. In the 43 children aged 54-66 months, the mean skin thickness was significantly higher in the upper than in the lumbar area (1.39 mm vs. 1.31 mm). In this study setting, the heterogeneity in skin thickness cannot be considered sufficient to indicate various microneedle lengths for various ages or injection sites.     

Photoaging of the skin and occupation: correlation between clinical ultrasound and histological findings

OBJECTIVES: We described the ultrasound (US) signs that can define occupational photoaging of the skin. We also studied the clinical importance of these signs, so as to aid the specialist in the diagnosis and evaluation of "anti-aging" treatments. PATIENTS AND METHODS: The dermis and hypodermis of 180 subjects (6 groups of 15 men and 15 women each), were studied with US test (echograph Sonora 400 MD). We used a 10 MHz probe and recorded the thickness and echogenicity of the dermis and hypodermis. US images were correlated with the histological findings of 60 patients. RESULTS: In skin not exposed to sunlight aging produces an increase in thickness and a reduction in echogenicity, whereas in photoaging there is a reduction in thickness and an increase in echogenicity of the skin. CONCLUSION: Photoaging produces an increase in elastic fibres and consequently hyperechogenicity of the dermis, while, in the advanced phase, the loss of collagen and elastic fibres justify the reduction in thickness and echogenicity of the dermis. These observations allow as to classify the US signs of the photoaging of the skin into four clinical/ultrasound stages.     

超声对活鼠胚胎心肌细胞凋亡影响的研究

目的 观察诊断级超声波对活鼠胚胎心肌细胞Bcl-2及Bax表达及其凋亡的影响。方法 采用孕14d的Wistar大鼠36只,分为6组,分别为2.5MHz照射10 min、7MHz照射10 min、10 min对照组、2.5MHz照射40 min、7MHz照射40 min、40 min对照组(7MHz探头,Isppa=227W/cm²,Ispta=385mW/cm²;2.5MHz探头,Isppa=94.5W/cm²,Ispta=15.6mW/cm2)。采用免疫组化检测胎鼠心肌Bax及Bcl-2的表达,用TUNEL法及电镜检测胎鼠心肌细胞的凋亡情况。结果 统计显示同一样本不同胚胎间差异无显著性(P>0.05)。7MHz照射40 min组胎鼠心肌组织Bcl-2(+),Bax蛋白阳性(+),2.5MHz照射40min组胎鼠心肌组织Bcl-2阳性(+),Bax阳性(-),7MHz照射10min组胎鼠心肌组织Bcl-2(+),Bax蛋白阴性(-),2.5MHz照射10 min组胎鼠心肌组织Bcl-2阳性(+),Bax阳性(-),两组对照组两者均为(-);TUNEL试验及电镜显示7MHz照射40 min组较其他组凋亡差异有显著性(P<0.05),其余各组与对照组之间差异无显著性(P>0.05)。结论 较高强度诊断级超声波较长时间辐照可导致胎鼠心肌细胞凋亡,Bcl-2及Bax在该过程中起调节作用,小剂量的超声波可以促进Bcl-2表达来抑制细胞凋亡。     

Dermal penetration and systemic distribution of 14C-labeled vitamin E in human skin grafted athymic nude mice

In vivo percutaneous penetration and tissue distribution of 14C-labeled vitamin E applied to human skin grafted onto athymic nude mice were determined. At 1 hr, mouse skin contained the highest level of radioactivity, followed by the muscle, blood, liver, lung, adipose tissue, spleen, kidney, brain, heart, and eyes. A linear increase with time in tissue radioactivity was observed throughout the 24 hr experimental period. At 4 and 24 hrs skin grafts were highly radioactive. At 4 hrs the epidermis and the upper portion of the dermis contained more radioactivity than the remaining portion of the dermis. In contrast, at 24 hrs the highest level of radioactivity was detected in the lower dermis. No radioactivity was detected in expired air while 0.2% of the dose was found in the urine. The data show that vitamin E does penetrate skin and that the dermis acts as a barrier or reservoir for this highly lipophilic compound.     

Skin physiology

This review article offers a brief overview of skin physiology, including the epidermis, dermis, basement membrane zone and the role of psychological stress. Skin is the largest organ; it is complex and multifunctional, containing many specialized cells that are adapted to different functions. Skin consists of a superficial layer (epidermis) that adheres closely to the deeper layer (dermis) via the basement membrane. Loose connective tissue and fat underlie the dermis. The epidermis is composed of stratified squamous epithelium, comprising layers of closely packed cells produced by cell division of the ‘basal’ cell layer (a single sheet of columnar cells at the lowest level of the epidermis). The dermis lies below the epidermis and supports it structurally and nutritionally. The basement membrane zone forms an adhesion complex between the dermis and epidermis, providing support for the basal cells to allow growth, multiplication and migration, and allowing nutrients and cells to cross from the dermis. Psychological stress may precipitate or aggravate chronic disorders of the skin.